Browsing by Autor "Alonso-Vega, Cristina"

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[Endemic level of congenital Trypanosoma cruzi infection in the areas of maternal residence and the development of congenital Chagas disease in Bolivia].
(2005) Torrico, Faustino; Alonso-Vega, Cristina; Suarez, Eduardo; Rodríguez, Patricia; Torrico, Mary-Cruz; Dramaix, Michele; Truyens, Carine; Carlier, Yves
In Bolivia, the prevalence of infection by T. cruzi in women in fertile age can vary between 20 and 60%. The present study made in the Maternity Germin Urquidi of Cochabamba - Bolivia, it has demonstrated, that 19.9% of the mothers who go to this hospitable center to be taken care of in the childbirth, they are carrying of the infection and that 4,6% of them, they are going to transmit, by transplacentaria route, the infection to its babies. Of the 71 children born with congenital Chagas, only 47,8 % present/display some type of alteration or of development(Apgar to 1 minute low, BPN, prematuridad, pathological dismadurez) or signs (SDR, hepatomegalia, esplenomegalia, neurological signs, cardiomegalia, anasarca, petequias). When investigating the effect of the differences in the vectorial density (low, medium and high) of the zone of maternal residence, on the transmission of the infection of the mother infected to the fetus, we concluded that the rate of transmission of the congenital infection of T. cruzi is not modified by the level of endemicidad of the zone of maternal residence. By another infected new born sides whose mothers reside in zones of high endemicidad present/display, most frequently and of significant way, Apgar to 1 minute < to 7, low weight when being born and prematuridad or an association of these alterations with respiratory syndrome of distress or anasarca, when one compares them with new born of resident mothers in the zones of loss or medium endemicidad, mortality in this group is greater. These results suggest calls to account it of the mothers, in areas of high endemicidad, she is associate with a serious increase in the risk of Disease of newborn severe and mortal congenital Chagas in.
[Immunological status of mothers infected with Trypanosoma cruzi].
(2005) Alonso-Vega, Cristina; Hermann, Emmanuel; Truyens, Carine; Rodriguez, Patricia; Torrico, Mary Cruz; Torrico, Faustino; Carlier, Yves
The mechanisms of congenital transmission of Chagas disease remain largely unknown. To better understand the role of maternal immunology during pregnancy in congenital Chagas transmission, we studied the cytokine production and the parasitic load in three groups of mothers: infected mothers who transmitted the disease to their babies (M+B+-), infected mothers who did not transmit the disease to their babies (M+B-) and not infected mothers as a control group (M-B-). M+B+ mothers produced less IFNgamma and more IL-10 than the M+B- mothers, and they are not able to produce IL-2. M+B+ mothers showed a higher parasitic load. These results, indicated that the congenital Chagas transmission is associated with an immunological imbalance and a high parasitic load in the M+B+ mothers.
[Integral treatment of congenital Chagas disease: the Bolivian experience ].
(2005) Suárez, Eduardo; Alonso-Vega, Cristina; Torrico, Faustino; Córdova, Marisol
We have analyzed the response to the treatment with benznidazol in newborns and nurslings in the Hospital Materno Infantil Germán Urquidi of Cochabamba, Bolivia, between 1999 and 2002. It is important an integral treatment of the nursling with a subsequent information directed to the family. The response was close to 100% when the treatment was correctly administrated. They were not adverse effects and the detected biochemical alterations did not present clinical significance.
Maternal Trypanosoma cruzi infection, pregnancy outcome, morbidity, and mortality of congenitally infected and non-infected newborns in Bolivia.
(2004) Torrico, Faustino; Alonso-Vega, Cristina; Suarez, Eduardo; Rodriguez, Patricia; Torrico, Mary-Cruz; Dramaix, Michèle; Truyens, Carine; Carlier, Yves
This work compares the results of two epidemiologic and clinical surveys on the consequences of maternal chronic Trypanosoma cruzi infection. They were conducted in 1992-1994 and 1999-2001 in the same maternity clinic in Bolivia, a country highly endemic for infection with this parasite. In both surveys, the materno-fetal transmission of parasites occurred in 5-6% of the infected mothers. Maternal chronic T. cruzi infection had no effect on pregnancy outcome and health of newborns when there was no materno-fetal transmission of parasites. Comparisons between the older and the more recent surveys highlighted significant reductions in frequencies of symptomatic cases (from 54% to 45%), Apgar scores < 7, and low birth weights and prematurity (from 32-50% to 6-16%) among congenitally infected babies. Neonatal mortality related to congenital Chagas disease also decreased from 13% to 2% in the interval between both studies. These results suggest that the decrease in poverty that has occurred in Bolivia between both surveys might have contributed to reduce the morbidity and mortality, but not the transmission rate of T. cruzi congenital infection, which remains a serious public health problem in this country.
New regimens of benznidazole monotherapy and in combination with fosravuconazole for treatment of Chagas disease (BENDITA): a phase 2, double-blind, randomised trial.
(2021) Torrico, Faustino; Gascón, Joaquim; Barreira, Fabiana; Blum, Bethania; Almeida, Igor C; Alonso-Vega, Cristina; Barboza, Tayná; Bilbe, Graeme; Correia, Erika; Garcia, Wilson; Ortiz, Lourdes; Parrado, Rudy; Ramirez, Juan Carlos; Ribeiro, Isabela; Strub-Wourgaft, Nathalie; Vaillant, Michel; Sosa-Estani, Sergio
BACKGROUND: Current treatment for Chagas disease with the only available drugs, benznidazole or nifurtimox, has substantial limitations, including long treatment duration and safety and tolerability concerns. We aimed to evaluate the efficacy and safety of new benznidazole monotherapy regimens and combinations with fosravuconazole, in the treatment of Chagas disease. METHODS: We did a double-blind, double-dummy, phase 2, multicentre, randomised trial in three outpatient units in Bolivia. Adults aged 18-50 years with chronic indeterminate Chagas disease, confirmed by serological testing and positive qualitative PCR results, were randomly assigned (1:1:1:1:1:1:1) to one of seven treatment groups using a balanced block randomisation scheme with an interactive response system. Participants were assigned to benznidazole 300 mg daily for 8 weeks, 4 weeks, or 2 weeks, benznidazole 150 mg daily for 4 weeks, benznidazole 150 mg daily for 4 weeks plus fosravuconazole, benznidazole 300 mg once per week for 8 weeks plus fosravuconazole, or placebo, with a 12-month follow-up period. The primary endpoints were sustained parasitological clearance at 6 months, defined as persistent negative qualitative PCR results from end of treatment, and incidence and severity of treatment-emergent adverse events, serious adverse events, and adverse events leading to treatment discontinuation. Primary efficacy analysis was based on the intention-to-treat and per-protocol populations and secondary efficacy analyses on the per-protocol population. Safety analyses were based on the as-treated population. Recruitment is now closed. This trial is registered with ClinicalTrials.gov, NCT03378661. FINDINGS: Between Nov 30, 2016, and July 27, 2017, we screened 518 patients, and 210 were enrolled and randomised. 30 patients (14%) were assigned to each treatment group. All 210 randomised patients were included in the intention-to-treat population, and 190 (90%) were included in the per-protocol population. In the intention-to-treat analysis, only one (3%) of 30 patients in the placebo group had sustained parasitological clearance at 6 months of follow-up. Sustained parasitological clearance at 6 months was observed in 25 (89%) of 28 patients receiving benznidazole 300 mg daily for 8 weeks (rate difference vs placebo 86% [95% CI 73-99]), 25 (89%) of 28 receiving benznidazole 300 mg daily for 4 weeks (86% [73-99]), 24 (83%) of 29 receiving benznidazole 300 mg daily for 2 weeks (79% [64-95]), 25 (83%) of 30 receiving benznidazole 150 mg daily for 4 weeks (80% [65-95]), 23 (85%) of 28 receiving benznidazole 150 mg daily for 4 weeks plus fosravuconazole (82% [67-97]), and 24 (83%) of 29 receiving benznidazole 300 mg weekly for 8 weeks plus fosravuconazole (79% [64-95]; p<0·0001 for all group comparisons with placebo). Six patients (3%) had ten serious adverse events (leukopenia [n=3], neutropenia [n=2], pyrexia, maculopapular rash, acute cholecystitis, biliary polyp, and breast cancer), eight had 12 severe adverse events (defined as interfering substantially with the patient's usual functions; elevated alanine aminotransferase [n=4], elevated gamma-glutamyltransferase [n=2], elevated aspartate aminotransferase [n=1], neutropenia [n=3], leukopenia [n=1], and breast cancer [n=1]), and 15 (7%) had adverse events that led to treatment discontinuation (most of these were in the groups who received benznidazole 300 mg daily for 8 weeks, benznidazole 300 mg once per week for 8 weeks plus fosravuconazole, and benznidazole 150 mg daily for 4 weeks plus fosravuconazole). No adverse events leading to treatment discontinuation were observed in patients treated with benznidazole 300 mg daily for 2 weeks or placebo. There were no treatment-related deaths. INTERPRETATION: Benznidazole induced effective antiparasitic response, regardless of treatment duration, dose, or combination with fosravuconazole, and was well tolerated in adult patients with chronic Chagas disease. Shorter or reduced regimens of benznidazole could substantially improve treatment tolerability and accessibility, but further studies are needed to confirm these results. FUNDING: Drugs for Neglected Diseases initiative (DNDi). TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.
[Serum levels for IgM and IgA antibodies to anti-trypanosoma cruzi in samples of blood from newborns from mothers with positive serology for Chagas disease].
(2005) Rodriguez, Patricia; Truyens, Carine; Alonso-Vega, Cristina; Flores, Amilcar; Cordova, Marisol; Suarez, Eduardo; Torrico, Faustino; Carlier, Yves
This study compares the levels of specific antibodies IgM and IgA for Chagas in samples of blood from newborns. Three groups of cord blood samples have been analysed: a group of 42 samples from newborns, displaying positive parasitemia, of seropositive mothers (M+B+), 68 samples from newborns with negative parasitemia whose mothers were seropositive (M+B-) and a group of 45 control newborns coming from mothers with negative serology for Chagas. From the 42 M+B+ samples with congenital Chagas disease, 81 and 82.9% displayed detectable levels of IgM and IgA antibodies, respectively In the M+B- group, 70.6 and 33.8% presented antibodies of IgM and IgA classes, respectively, whereas in the control group M-B-, we detected 6% and 11.1% of IgM and IgA antibodies, respectively. The calculated sensitivity of detection of congenital cases using IgM or IgA antibodies was of 82.9% and 80.9% respectively, whereas the specificity of detection was of 29.4% for IgM antibodies and of 66.1% for IgA antibodies.
Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled trial.
(2018) Torrico, Faustino; Gascon, Joaquim; Ortiz, Lourdes; Alonso-Vega, Cristina; Pinazo, María-Jesús; Schijman, Alejandro; Almeida, Igor C; Alves, Fabiana; Strub-Wourgaft, Nathalie; Ribeiro, Isabela
BACKGROUND: Chagas disease is a major neglected vector-borne disease. In this study, we investigated the safety and efficacy of three oral E1224 (a water-soluble ravuconazole prodrug) regimens and benznidazole versus placebo in adult chronic indeterminate Chagas disease. METHOD: In this proof-of-concept, double-blind, randomised phase 2 clinical trial, we recruited adults (18-50 years) with confirmed diagnosis of Trypanosoma cruzi infection from two outpatient units in Bolivia. Patients were randomised with a computer-generated randomisation list, which was stratified by centre and used a block size of ten. Patients were randomly assigned (1:1:1:1:1) to five oral treatment groups: high-dose E1224 (duration 8 weeks, total dose 4000 mg), low-dose E1224 (8 weeks, 2000 mg), short-dose E1224 (4 weeks + 4 weeks placebo, 2400 mg), benznidazole (60 days, 5 mg/kg per day), or placebo (8 weeks, E1224-matched tablets). Double-blinding was limited to the E1224 and placebo arms, and assessors were masked to all treatment allocations. The primary efficacy endpoint was parasitological response to E1224 at the end of treatment, assessed by PCR. The secondary efficacy endpoints were parasitological response to benznidazole at end of treatment, assessed by PCR; sustainability of parasitological response until 12 months; parasite clearance and changes in parasite load; incidence of conversion to negative response in conventional and non-conventional (antigen trypomastigote chemiluminescent ELISA [AT CL-ELISA]) serological response; changes in levels of biomarkers; and complete response. The primary analysis population consisted of all randomised patients by their assigned treatment arms. This trial is registered with ClinicalTrials.gov, number NCT01489228. FINDINGS: Between July 19, 2011, and July 26, 2012, we screened 560 participants with confirmed Chagas disease, of whom 231 were enrolled and assigned to high-dose E1224 (n=45), low-dose E1224 (n=48), short-dose E1224 (n=46), benznidazole (n=45), or placebo (n=47). Parasite clearance was observed with E1224 during the treatment phase, but no sustained response was seen with low-dose and short-dose regimens, whereas 13 patients (29%, 95% CI 16·4-44·3) had sustained response with the high-dose regimen compared with four (9%, 2·4-20·4) in the placebo group (p<0·0001). Benznidazole had a rapid and sustained effect on parasite clearance, with 37 patients (82%, 67·9-92·0) with sustained response at 12-month follow-up. After 1 week of treatment, mean quantitative PCR repeated measurements showed a significant reduction in parasite load in all treatment arms versus placebo. Parasite levels in the low-dose and short-dose E1224 groups gradually returned to placebo levels. Both treatments were well tolerated. Reversible, dose-dependent liver enzyme increases were seen with E1224 and benznidazole. 187 (81%) participants developed treatment-emergent adverse events and six (3%) developed treatment-emergent serious adverse events. Treatment-emergent adverse events were headaches, nausea, pruritus, peripheral neuropathy, and hypersensitivity. INTERPRETATION: E1224 is the first new chemical entity developed for Chagas disease in decades. E1224 displayed a transient, suppressive effect on parasite clearance, whereas benznidazole showed early and sustained efficacy until 12 months of follow-up. Despite PCR limitations, our results support increased diagnosis and access to benznidazole standard regimen, and provide a development roadmap for novel benznidazole regimens in monotherapy and in combinations with E1224. FUNDING: Drugs for Neglected Diseases initiative.
Usefulness of Serial Blood Sampling and PCR Replicates for Treatment Monitoring of Patients with Chronic Chagas Disease.
(2019) Parrado, Rudy; Ramirez, Juan Carlos; de la Barra, Anabelle; Alonso-Vega, Cristina; Juiz, Natalia; Ortiz, Lourdes; Illanes, Daniel; Torrico, Faustino; Gascon, Joaquim; Alves, Fabiana; Flevaud, Laurence; Garcia, Lineth; Schijman, Alejandro G; Ribeiro, Isabela
This work evaluated a serial blood sampling procedure to enhance the sensitivity of duplex real-time quantitative PCR (qPCR) for baseline detection and quantification of parasitic loads and posttreatment identification of failure in the context of clinical trials for treatment of chronic Chagas disease, namely, DNDi-CH-E1224-001 (ClinicalTrials.gov registration no. NCT01489228) and the MSF-DNDi PCR Sampling Optimization Study (NCT01678599). Patients from Cochabamba (n = 294), Tarija (n = 257), and Aiquile (n = 220) were enrolled. Three serial blood samples were collected at each time point, and qPCR triplicates were tested for each sample. The first two samples were collected during the same day and the third one 7 days later. A patient was considered PCR positive if at least one qPCR replicate was detectable. Cumulative results of multiple samples and qPCR replicates enhanced the proportion of pretreatment sample positivity from 54.8% to 76.2%, 59.5% to 77.8%, and 73.5% to 90.2% in Cochabamba, Tarija, and Aiquile cohorts, respectively. This strategy increased the detection of treatment failure from 72.9% to 91.7%, 77.8% to 88.9%, and 42.9% to 69.1% for E1224 low-, short-, and high-dosage regimens, respectively, and from 4.6% to 15.9% and 9.5% to 32.1% for the benznidazole arm in the DNDi-CH-E1224-001 and MSF-DNDi studies, respectively. The addition of the third blood sample and third qPCR replicate in patients with nondetectable PCR results in the first two samples gave a small, non-statistically significant improvement in qPCR positivity. No change in clinical sensitivity was seen with a blood volume increase from 5 to 10 ml. The monitoring of patients treated with placebo in the DNDi-CH-E1224-001 trial revealed fluctuations in parasitic loads and occasionally nondetectable results. In conclusion, a serial sampling strategy enhanced PCR sensitivity to detecting treatment failure during follow-up and has the potential for improving recruitment capacity in Chagas disease trials, which require an initial positive qPCR result for patient admission.
Vinchucas, Trypanosomas y demás familia: Nociones sobre la enfermedad de Chagas
(RevActaNova., 2002) Alonso-Vega, Cristina